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Dave Chiswell and the Science of Success

Kymab CEO, Dave Chiswell, called 'one of the godfathers of the biotech industry' by the FT, explains his desire and drive for success.

In an interview in early 2015, Dave Chiswell, then Chairman of Kymab, was asked what he saw as the company's future. His answer was simple, direct.

"We will be a Europe-based, global pharmaceutical company: we want to be the European Genentech."

From many spokespeople, this might sound like so much smoke-blowing. But Dave is usually measured - and he has a track record to back up his assertions. He knows how to grow a company and he knows how to strike a deal.

As Dave takes the reins at Kymab now as CEO, he explains his clear ideas on the dynamics of his chosen arena — the business of making medicines.

Why Kymab? Why now?

After founding the UK's most successful biotechs - bought by AstraZeneca in 2008 for $1.3bn - as well as a serial career on the Boards of many others in addition to a stint as Chair of the UK's BioIndustry Association, what made him want to take the CEO role at a new and growing biotech company?

"To take the reins of Kymab was too good an opportunity to pass on. I did consider it carefully - what could I bring, how could we steer Kymab, but the real answer is I didn't hesitate.

"Kymab has the vision, the plans, the partners and the components in place to be a remarkable success. I really had to be part of turning that potential into reality."

His appointment is a real coup for Kymab and a strong commentary on the future of the company. Dave has the track record to develop a company that produces medicines to satisfy markets, to enrich partnerships and to heal patients.

CAT and mouse games

In 1989, Amersham (now part of GE Healthcare) decided to close its central research lab where Dave led the search for future products, among which was a strand looking at producing humanised antibodies. Dave had discussed this area with Greg Winter, a leading immunologist at the Medical Research Council Laboratory of Molecular Biology and, with the closure of the Amersham programmes, they decided together to set up Cambridge Antibody Technology.

"We reasoned that our shared research aims could lead rapidly to technologies to produce humanised antibodies using bacterial viruses - phages - as tools to create fully human antibodies. We were really optimistic we could turn this around quickly."

"Scientifically we got off to a flying start with John McCafferty hot benching in Greg's lab and virtually his first experiments demonstrated that phage display would work for antibodies. But it wasn't an auspicious start financially," remembers Dave. "We were running on very little money and we rented one off the first available labs on the Babraham Campus. Today, it's a renowned biotech hub - and home to Kymab - but back then we had had a few labs in what were essentially 1940s sheds!"

The technology of CAT - using phages to display proteins - quickly advanced and resulted in a Nature paper within 12 months. Nevertheless, the first three years demanded rapid development of the science if it was to realise its potential for useful human antibodies.

Dave's experience at Amersham brought a strong sense of the financial imperative to bring income as early as possible. Under his guidance, CAT built a business model that has become standard practice in the biotech arena.

In their 2010 review "Exploding the Myths of UK Innovation Policy: How 'Soft Companies' and R&D Contracts for Customers Drive the Growth of the Hi-Tech Economy", Connell and Probert, from the University of Cambridge, praise CAT as a biotechnology trailblazer - the first company to build its business around partnerships with pharmaceutical companies founded on milestone payments, taking the business forward in a sustainable fashion.

The fledgling company gained around $1.4M in start-up funds and focussed initially on R&D contracts and specific kits that would realise a revenue stream. Remarkably, the company operated at an operating profit only four years after founding. That wasn't to last of course.

"Our contract work was an important source of funding to allow us to develop the pipeline that we could fill through a range of deals," says Dave. "Without our business heads on, we would have struggled to find the R&D space to come up with Humira®."

Humira® (Adalimumab) was the world's biggest-selling prescription drug in 2015 at $14 bn; it was discovered and developed in a CAT programme collaborating with BASF that was signed in 1993 (the product is now owned by Abbvie who acquired BASF). The deal was carefully staged with milestone payments against targets.

"The challenges were really stringent, but we knew we could realise a good return only if we took a good part of the risk," explains Dave. "We put our money, our minds and our people where our mouth was and managed the risk into acceptable packages."

That early success gave CAT credibility, ensuring it could demand higher fees for up-front access. Meanwhile, the continuing model of mixed income streams ensured stability and allowed CAT to develop a strong pipeline. At its takeover by AstraZeneca, CAT had revenues of almost $0.5 bn.

Making mice make medicines

Today, Dave has just taken permanent hold of the reins at what seems a mouse-based descendant of CAT — an antibody company working together with and in competition with some of the largest and some of the most nimble actors in the therapeutic antibody arena.

Why pitch back into that? Dave believes that Kymab's skills, partnerships and technologies mean it can succeed in these sectors.

"Some might talk about facing challenges or testing yourself. I don't need challenges - though I relish facing them - but I do really believe in this company and what it is doing.

"For me, Kymab is a tremendous opportunity to do something really special. If I didn't have that belief that we can succeed at Kymab, I wouldn't be here."

Targeting diversity

CAT made hugely successful antibodies using phages to produce the antibody proteins. Kymab's platform differs from CAT's as much as a surround-sound widescreen TV does from the mechanical TV invented by John Logie Baird. Kymab's antibodies are produced as part of a functioning human immune system, with the advantages and subtleties in protein production that brings.

"Because Kymab's antibodies are produced by a human immune system, our products don't need significant antibody engineering or optimisation in vitro," says Dave. "We can reduce development time significantly - by three to six months.

"Our human immune system also delivers a more diverse antibody set - meaning we are more likely to find an effective lead antibody. We get the double bonus of a diverse repertoire: we are also more likely to produce high-affinity antibodies - antibodies that work better. In addition we have a model of the human antibody response to vaccine candidates which we believe can make a big difference to the vaccines of the future."

Dave argues that these advantages set Kymab apart from competitors, with the potential to rapidly fill its own pipeline and to support the search by partners for effective treatments.

Teams, technologies, talent and targets

With tens of thousands of possible targets and trillions of antibodies that might recognise them, Kymab's R&D challenges seem formidable, And it is working in some fiercely competitive arenas - immuno-oncology, blood disease, immunology and infectious disease - where antibodies are in the vanguard of the search for new treatments.

Immuno-oncology, harnessing the body's defences to attack cancer cells, represents today's most promising area for new cancer medicines that engage the patient's own immune system to mount an effective response against tumours.

A common feature of cancers is that peptides - protein fragments - are displayed on the cell surface. Often the peptides would normally be restricted to the inside of the cell, so their external presentation is a maker of a cancer cell and a possible avenue for therapeutic attack.

Cancer cell genomes change all the time and the displayed peptides are often mutated and changing. Ideally, an antibody should recognise the regions of normal peptide that are unchanged through the cancer development. An effective antibody against the cancer cell marker could be a cancer cell killer.

A major focus for Kymab and its partners, it is pursued by all major pharmaceutical companies: all expect it to dramatically improve patient survival and quality of life.

In such competition, you need the brightest minds and Dave speaks enthusiastically of the group Kymab has assembled.

"Building the best team is a scientific process and we have a team here that has world-class experience in developing antibody therapeutics: our leadership team includes experience with CAT, Medimune UCB, Medarex, Micromet, GSK, AstraZeneca, Serono, and the Sanger Institute.

"We've also recently recruited genuine leaders to manage our key areas; their desire to join the Kymab team is a tremendous validation of the value of our R&D programme."

Under the guidance of the leadership team, Kymab has rapidly generated candidate-quality antibodies directed against both novel and established immuno-oncology targets. In the coming months, the programmes in development will feed the pipeline with a rich suite of highly differentiated antibody-based therapeutics.

Kymab's therapeutic approach of delivering diverse, high-affinity antibodies also serves well in the company's other therapeutic areas: immunology, blood diseases and infectious disease. In each of these areas, the biggest challenge is finding the antibody target that is most effective in influencing the disease, whether through a therapeutic drug or a vaccine.

The confidence that Kymab has in its platform and pipeline is endorsed by its funders: it has attracted $120M from investors the Bill & Melinda Gates Foundation, the Wellcome Trust, Woodford Investments and Malin plc.

"At the time, the Bill & Melinda Gates Foundation investment of US$20M was their first investment in a biotech company," says Dave. It is clearly a thought that delights him, not from pride, but from a feeling of validation.

"Kymab has a technology and opportunity that excites us and excites our partners."

MRC, CPS, UCLA, ICRF, GE, CAT, BIA: a life in acronym

I have to admit that I have known Dave for more than 40 years: we did our PhDs together at the MRC Institute of Virology in the 1970s. Even then, he had a flair for business.

Together with another student, we ran a short-lived car-repair business, which we called CPS Autos. Dave, cannily, invested the most and took the biggest share of the returns when the Institute's Head (quite reasonably) called time on the venture. Dave even, unimaginably, bought and sold an aged Triumph TR6 at 50% profit over six months.

Even as a young man, he could see the business opportunity and maximise returns.

After his PhD on retroviruses, he did a postdoc on the same topic at the prestigious University of California, Los Angeles, before staff positions at the Imperial Cancer Research Fund (now Cancer Research UK).

He joined Amersham (now part of GE Health) in 1981, developing kits and reagents that would make bench science better.

"During my PhD, we were making the restriction enzymes that cut DNA for cloning from bacterial cells. In my postdocs there were students and other lab staff preparing their own kits to do their research. This seemed like a bad use of their time and we wanted to provide high-quality, validated reagents that just worked."

Then, after almost 10 years, Amersham closed the development division — and CAT was born.

Profit before patient?

Biotech and pharma have been heavily criticised recently for the prices charged for their treatments, especially after some significant price hikes through that period. This thorny issue is unlikely to disappear: health economies are under pressure.

Meanwhile, patient groups are more informed and more demonstrative in their demands for access to treatment, above that Dave welcomes.

As he said before the UK House of Commons Health Committee in 2005: "…patients are going to know more about their conditions… Wherever you are in the medical world, the patient should know more. That is going to be to the benefit of us all in the long run."

There is a demand, but can Kymab produce the medicines that people need? And can that be at a price that health providers can afford?

At the same hearing on the Influence of the Pharmaceutical Industry, Dave declared that "We are all patients, or we all will be, and, if we focus on something which is good for the patient, that is good for the industry and it is good for the public health Unless you produce something which is good for patients somewhere, then your business is going to be limited."

He has also argued that regulation and oversight could be more efficient: he suggests that rigorous safety and efficacy assessment is essential, but could work in a more effective way, saving time and costs.

The areas where Kymab currently makes its contribution are the less expensive components of drug development and Dave sees Kymab as a lean, efficient and effective developer of potential new therapies and vaccines.

He knows the big costs lie ahead, as Kymab moves towards trials. And that time is not far.

Close to the clinic?

"We hope to get two projects into clinical trials each year from 2017 - only 12 months away," says Dave with confidence. "Our pipeline will produce candidates across all our therapeutic areas, with the first likely to be in haematology and auto-immune disease.

"We're really excited about progress in our vaccine work - and across all our areas."

Kymab has developed a strong underpinning of intellectual property and a portfolio of world-leading development partners based its discovery platform. This platform has also enabled Kymab to develop a rich pipeline of product opportunities with broad applications in challenging and important areas. Now it aims to drive its first-in-class therapeutic human monoclonal antibodies towards first-in-human studies, while continuing to add new product opportunities.

Traditionally, many candidates fail the development and clinical examinations: there are many familiar images of 10,000 compounds being filtered to only one in the funnel of preclinical and clinical trials. Kymab hopes to address that in part by optimising the candidates it sends.

But it also needs funding: Dave is bullish about Kymab's experience, and recent significant investment in UK companies, believing that investors appreciate that drip-feed funding will not produce UK-based, international companies.

"Our ambition has to be success of the type Genentech or Amgen have achieved, in all senses. For an investor it means we have to deliver returns on their faith in us over a reasonable time frame. For our partners, it means we are a strong, effective and efficient collaborator who delivers our part of the bargain.

"For patients, it means we provide new treatments in difficult disease indications because our team at Kymab can harness the power of our technology in the war on disease.

"If we strike our enemies as hard as we can, we can win many of our battles."

Bibliography and links

Connell D and Probert J (2010). Exploding the Myths of UK Innovation Policy: How 'Soft Companies' and R&D Contracts for Customers Drive the Growth of the Hi-Tech Economy. Centre for Business Research, University of Cambridge, UK. PDF article

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Since our founding in 2010, Kymab has raised $220 million in equity financing from leading investors to enable us to develop our unique antibody platforms and create a portfolio of therapeutic antibody assets.